[Distribution in the body of animals of the carbonic acid taken up from a carbonic acid bath].
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The ionization kinetics of carbon acids are slow relative to those of classical acids and bases. Phenindione (2-phenyl-1,3-indandione) is a 1,3-diketone carbon acid of macroscopic experimental pKa 4.09 at 25 degrees and ionic strength 0.1. The ionization kinetics of phenindione were determined at an ionic strength of 0.1 and 25 degrees using stopped-flow spectrophotometry and a pH jump technique. A log k'obs-pH profile for the approach to the ionization equilibrium was determined, and a mechanism consistent with the profile was postulated. The percent enol versus diketo form of phenindione and the pKaenol and pKadiketo were calculated from the kinetic data. Phenindione acid deprotonation kinetics by various oxygen and nitrogen bases suggested that, with bases of pKa 4.7--8.5 and in the pH 5--8.5 range, the acidic phenindione proton as approximately 45% transferred in the rate-determining transition state.
A rise in the carbonic acid and pH level in rat blood determines an increase in oxidative properties of the liver cell cytoplasm. Simultaneously the content of alpha-ketoglutarate, isocitrate, glutamate, alpha-glycerophosphate, dihydroxyacetone phosphate, pyruvate, lactate, malate increases and the level of glucose, glutamine and ammonia decreases. The in vitro experiments showed that the rise in the level of carbonic acid in the incubation medium from 10 up to 40 mM under all the studied values of pH (7.2, 7.4, 7.6) stimulates formation of dihydroxyacetone phosphate, malate, pyruvate, alpha-ketoglutarate (by 1.5-2.0 times). The same regularity is observed for lactate and glutamate at pH 7.4 and 7.6. The increase in the level of carbonic acid under the all studied values of pH produces a 1.5-fold decrease in the ammonia concentration.
A rise in the level of carbonic acid in animal blood at practically unchanged pH causes an increase in the value of free [NAD+]/[NADH] and [NADP+]/[NADPH] ratios in the liver cells cytoplasm. The increase in the oxidizing power of the liver cells cytoplasm is observed against a background of a rise in both the total level of keto-acids in blood and concentration of pyruvate oxaloacetate and alpha-ketoglutarate in the liver and kidneys of animals. The level of lactate, glutamate and citrate in these tissues also grows. The level of ketonic bodies in blood of the animals with a higher concentration of carbonic acid is somewhat lower than that in the animals with a lower concentration of HCO3 and CO2 in blood.
The ionization kinetics of 1.3-diketone carbon acids are slow relative to those of classical acids and bases. The ionization kinetics of three 4'-substituted 2-phenyl-1,3-indandiones, 4'-chloro-, 4'-methoxy-, and 2-phenyl-1,3-indandione itself, were studied at 25 degrees and ionic strength 0.1 using stopped-flow spectrometry and a pH jump technique. A log k'obs-pH profile for the approach to the ionization equilibrium was consistent with a reaction scheme postulated earlier for the ionization of another carbon acid, phenylbutazone. The percent enol versus diketo form of the acids and the pKaenol and pKadiketo were calculated from the kinetic data. Hammett plots of the various kinetic and equilibrium constants supported a mechanism for acid deprotonation consistent with proton abstraction being the predominant process when very weak bases such as water were the proton acceptors. Desolvation effects and the work required to get the two reacting molecules together in the correct configurations predominated when the proton abstraction was by stronger proton acceptors.
The first apparent dissociation constant of carbonic acid, pK'1, of plasma and red cells was determined on venous blood of ten healthy, adult, male, human subjects. pH and PCO2 of plasma and red cells were analyzed electrometrically and a micromanometric method was used for the determination of total carbon dioxide content. Erythrocyte carbamino hemoglobin levels were estimated and used for the correction of erythrocyte pK'1. Each blood sample was subjected to the following regimen before centrifugation, 1) As drawn from the antecubital vein, 2) Oxygenated with a 5% CO2, O2 balance gas mixture, and 3) Reduced with a 5% CO2, N2 balance gas mixture. pK'1 of plasma and red cells are presented: (see article). The consistently larger values for red cell pK'1 than the respective plasma data may be attributed to the greater amount of carbamino hemoglobin concentration present in the erythrocytes. A simplified method for the calculation of erythrocyte bicarbonate concentration using the experimentally determined red cell pK'1 value has been formulated. The method involves the use of a regression equation relating plasma and red cell pH, the equivalence of plasma and red cell PCO2, along with the experimentally determined red cell pK'1.
Recently a new enzymic carboxylation reaction has been discovered at the final-step of prothrombin and other proteins synthesis. The presence of the unique amino acid, gamma-carboxyglutaminic acid, is established and its structure is determined. The role of the acid is shown in Ca2+ fixation in the known proteins, playing an important role in the blood coagulation processes, and in some new proteins participating in the tissue calcification. Data are systematized on the necessity of vitamin K in the new reaction of the carbonic acid fixation under conditions of its in vitro simulation.
A dependence is established for the activity of NADP-dependent isocytrate dehydrogenase and malate dehydrogenase as well as of NAD-malate dehydrogenase on the carbonic acid level. When the biocarbonate concentration in rabbit blood and tissues rise, the activity of cytoplasmic NADP-isocytrate dehydrogenase and NADP-malate dehydrogenase of the liver lowers. The analogous regularity is observed in the in vitro experiments when the bicarbonate concentrations in the medium rises up to 40 mM (within the physiological limits). The activity of NAD-malate dehydrogenase in the soluble fraction of the rabbit liver and kidney increases with the bicarbonate level within the same limits. The found dependence was confirmed in experiments with the enzyme crystalline preparations.
Strains of Mycobacterium tuberculosis were obtained from 65 patients with pulmonary tuberculosis resident in Uganda, and from pulmonary and extrapulmonary tuberculosis in 42 British patients of European ethnic stock and in 67 Asian immigrants, often from Uganda, resident in Britain. The bacteriophage-type patterns of the African, British and Asian strains were different. The pattern for the Asian strains resembled that found previously in patients from South India, suggesting that there has been little interchange of organisms between the Asian community and the African and British communities alongside whom they have lived. The patterns for pulmonary and extra-pulmonary tuberculosis were similar. Strains of bacteriophage type 1, mainly obtained from Asians, were characterized by a greater susceptibility to the bactericidal activity of hydrogen-peroxide and/or a greater sensitivity to thiophen-2-carbonic acid hydrazide than strains of other types.
Perfusion of the small intestine of anesthetized cats with a solution imitating metabolic acidosis (pH = 7.3; [HCO-3] = =20.2 mM; PCO2 = 38 mm Hg) produced a threshold reflex increase in the blood pressure. The subsequent decrease of [HCO-3] to 3.2 mM and pH to 6.5 evoked a gradual raise of the blood pressure followed by a sharp increase of pressor reflexes amplitude within the range of pH 6.5--6.3. Solutions imitating metabolic acidosis (pH = 7.1; [HCO-3] = 12.7 mM) were found to increase the concentration of H+ ions in the outflow perfusate and blood pressure to larger extent than solutions imitating respiratory acidosis (pH = 7.1; PCO2 = 75 mm Hg). If the solution pH was held constantly at 7.4 by simultaneous decreasing PCO2 and [HCO-3] by a factor of two, a reflex increase in the blood pressure and decrease of perfusate pH had no effect either on blood pressure or perfusate pH. The data obtained suggest that one of the primary determinants of different responses of the tissue chemoreceptors to CO2 is the interstitial pH.
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1. A-V differences and milk concentrations of respiratory gases, pH, HCO3 and H2CO3 have been measured in lactating goats and cows. 2. The pH and [HCO3 minus] of milk were significantly lower than those of plasma while milk PCO2 was virtually identical to that of mammary venous blood. [H2CO3+ dissolved CO2] was similar in milk and blood. 3. 14-C (from injected [14-C]HCO3 minus was found to cross the mammary epithelium in both directions. 14-C also passed across the duct epithelium and since this epithelium has previously been shown to be impermeable to ions it is argued that 14-C crossed in an unionized form, i.e. as CO2 and/or H2CO3. 4. Hourly milking with the aid of oxytocin raised milk pH, [HCO3 minus], [H2CO3], [Na] and E1Cl], and lowered [K], [lactose] and [phosphate]. These effects are discussed in relation to the hypothesis proposed previously for the action of oxytocin on milk composition. 5. A scheme for the distribution and movements of CO2, H2CO3 and HCO3 minus between extracellular fluid and milk is suggested, and discussed in relation to Cl minus transport.
In cats in barbiturate anesthesia extracellular pH and potassium were continously recorded from brian cortex by implanted microelectrodes. Implantation of the electrodes preserved the low permeability of the blood-brain-barrier to HCO3-minus and H+ions as indicated by the development of brain acidosis by I.V. injection of HCO3-minus. Acetazolamide (25 mg/kg) i.v. was followed by a marked brain acidosis which after 10 min had progressed to a drop in pH of 0.203 plus or minus 0.046 (x bar plus or minus S.D., n equals 8). The slowness ofthe development of acidosis points to a direct effect of the carbonic anhydrase inhibition on the brain tissue. As a further support for this conclusion was considered the finding of a prolonged response time of brain pH to HCO3-minus i.v. to CO2-minus inhalation, and to hyperventilation after the acetazolamide inhibtion. No changes in brain extracelllular potassium were found.
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33 different adamntyl amidines containing four different structural types were synthesized and checked for virostatic activity. The activity of compounds of type II seems to originate in their ability to form H-bonds. The strength of antiviral activity is at least partly determined by the electronic effects of substituents at the benzene ring.